Efficacy and Safety of NestaCell® in Huntington's Disease

Summary

Huntington's disease (HD) is a rare neurodegenerative condition caused by increased CAG trinucleotide repeats in the HTT gene, on chromosome 4. The estimated global prevalence is 2.71 cases per 100,000 inhabitants. In Brazil, it is estimated that 13,000 to 19,000 people carry the gene and 65,000 to 95,000 are descendants at risk. HD usually manifests itself in the fourth decade of life with motor, cognitive and behavioral symptoms, such as chorea. This condition profoundly affects quality of life and there is no treatment that can modify its course. Tetrabenazine is the only medication approved to control chorea. A partnership between the Butantan Institute and Cellavita investigates the use of Human Dental Pulp Stem Cells (hDPSCs) to treat HD. NestaCell® was developed, a product based on these cells, which express high levels of BDNF, an important neurotrophic factor for neuronal survival. Preclinical tests showed that NestaCell® is distributed to several organs, including the central nervous system, being well tolerated in toxicological tests in rats. In phase I (SAVE) and phase II (ADORE) clinical trials, NestaCell® was administered to patients with HD. The results indicated a significant improvement in motor scores and functional capacity compared to placebo, demonstrating a clinically significant benefit. NestaCell® also presented a good safety and tolerability profile, with few adverse events related to the product. The results support the conclusion that NestaCell® is safe and well tolerated in HD patients, within the doses tested.

Timeline

Start

2024-06-08

Primary completion

2025-09-08

Completion

2026-02-09

Publications

• Background ABH - Associação Brasil Huntington. p. Perguntas Frequentes. Disponível em: https://abh.org.br/perguntas-frequentes/. Acesso em: 19/12/2022.
• Background BARRETO, R. D. R. Características da Disfunção Congnitiva na Doença de Huntington. Orientador: JANUÁRIO, D. C. 2009. 87 f. (Mestre) - Faculdade de Medicina, Universidade de Coimbra.
• Background Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch Med Sci. 2015 Dec 10;11(6):1164-78. doi: 10.5114/aoms.2015.56342. Epub 2015 Dec 11.
• Background Baydyuk M, Xu B. BDNF signaling and survival of striatal neurons. Front Cell Neurosci. 2014 Aug 28;8:254. doi: 10.3389/fncel.2014.00254. eCollection 2014.
• Background Benedict RH, DeLuca J, Phillips G, LaRocca N, Hudson LD, Rudick R; Multiple Sclerosis Outcome Assessments Consortium. Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis. Mult Scler. 2017 Apr;23(5):721-733. doi: 10.1177/1352458517690821. Epub 2017 Feb 16.
• Background BENTON, A. L.; HAMSHER, K. S.; SIVAN, A. B.; PSYCHOLOGICAL ASSESSMENT RESOURCES, I. Multilingual Aphasia Examination, Third Edition: Manual of instructions. PAR, 1978.
• Background Biglan KM, Zhang Y, Long JD, Geschwind M, Kang GA, Killoran A, Lu W, McCusker E, Mills JA, Raymond LA, Testa C, Wojcieszek J, Paulsen JS; PREDICT-HD Investigators of the Huntington Study Group. Refining the diagnosis of Huntington disease: the PREDICT-HD study. Front Aging Neurosci. 2013 Apr 2;5:12. doi: 10.3389/fnagi.2013.00012. eCollection 2013.
• Background Chen J, Marks E, Lai B, Zhang Z, Duce JA, Lam LQ, Volitakis I, Bush AI, Hersch S, Fox JH. Iron accumulates in Huntington's disease neurons: protection by deferoxamine. PLoS One. 2013 Oct 11;8(10):e77023. doi: 10.1371/journal.pone.0077023. eCollection 2013.
• Background Dorsey ER, Beck CA, Darwin K, Nichols P, Brocht AF, Biglan KM, Shoulson I; Huntington Study Group COHORT Investigators. Natural history of Huntington disease. JAMA Neurol. 2013 Dec;70(12):1520-30. doi: 10.1001/jamaneurol.2013.4408.
• Background FDA. Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular and Gene Therapy Products. pp. 27.
• Background Frank S, Testa C, Edmondson MC, Goldstein J, Kayson E, Leavitt BR, Oakes D, O'Neill C, Vaughan C, Whaley J, Gross N, Gordon MF, Savola JM; Huntington Study Group/ARC-HD Investigators and Coordinators. The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study. CNS Drugs. 2022 Nov;36(11):1207-1216. doi: 10.1007/s40263-022-00956-8. Epub 2022 Oct 15.
• Background GAMARRA, L.; CINTRA, L.; GÁRATE, A. P. Relatório Final do Estudo de Biodistribuição do Produto NestaCell®. Centro de Experimentação e Treinamento em Cirurgia (CETEC) do Instituto Israelita de Ensino e Pesquisa Hospital Albert Einstein, p. 72. 2022.
• Background Unified Huntington's Disease Rating Scale: reliability and consistency. Huntington Study Group. Mov Disord. 1996 Mar;11(2):136-42. doi: 10.1002/mds.870110204.
• Background JANUÁRIO, C. Doença de Huntington. Onde estamos agora? 2011. 148 f. (Doutor) -, Universidade de Coimbra.
• Background Muller M, Leavitt BR. Iron dysregulation in Huntington's disease. J Neurochem. 2014 Aug;130(3):328-50. doi: 10.1111/jnc.12739. Epub 2014 May 28.
• Background Niu L, Ye C, Sun Y, Peng T, Yang S, Wang W, Li H. Mutant huntingtin induces iron overload via up-regulating IRP1 in Huntington's disease. Cell Biosci. 2018 Jul 4;8:41. doi: 10.1186/s13578-018-0239-x. eCollection 2018.
• Background PATTERSON, J. Verbal Fluency. In: KREUTZER, J. S.;DELUCA, J., et al (Ed.). Encyclopedia of Clinical Neuropsychology. New York, NY: Springer New York, 2011. p. 2603-2606.
• Background Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N. The incidence and prevalence of Huntington's disease: a systematic review and meta-analysis. Mov Disord. 2012 Aug;27(9):1083-91. doi: 10.1002/mds.25075. Epub 2012 Jun 12.
• Background Resolução CNS nº 466. Brasília: Conselho Nacional de Saúde 2012.
• Background Resolução RDC n°508. Brasilia: Conselho Nacional de Saúde 2021.
• Background SPREEN, O.; SPREEN, B. P. P. O.; STRAUSS, E.; STRAUSS, P. P. E. A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary. Oxford University Press, USA, 1998. 9780195100198.
• Background Tumas V, Camargos ST, Jalali PS, Galesso Ade P, Marques W Jr. Internal consistency of a Brazilian version of the unified Huntington's disease rating scale. Arq Neuropsiquiatr. 2004 Dec;62(4):977-82. doi: 10.1590/S0004-282X2004000600009. Epub 2004 Dec 15.
• Background Walker FO. Huntington's disease. Lancet. 2007 Jan 20;369(9557):218-28. doi: 10.1016/S0140-6736(07)60111-1.
• Background Wenceslau CV, de Souza DM, Mambelli-Lisboa NC, Ynoue LH, Araldi RP, da Silva JM, Pagani E, Haddad MS, Kerkis I. Restoration of BDNF, DARPP32, and D2R Expression Following Intravenous Infusion of Human Immature Dental Pulp Stem Cells in Huntington's Disease 3-NP Rat Model. Cells. 2022 May 17;11(10):1664. doi: 10.3390/cells11101664.

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